Molecular imaging brings precision surgery to the OR

Over the past several decades, imaging techniques such as computed tomography, magnetic resonance imaging and positron emission tomography have greatly improved the early detection of cancer. But cancer survival often relies on complete tumor removal during surgical resection. The major obstacle to achieving this goal has been a surgeon’s ability to distinguish between tumor tissue and normal tissue during surgery, relying on eyesight and touch to determine tumor margins.

“It is unfortunate that surgeons must rely solely on their own eyesight to see cancer in the operating room,” said Sam Gambhir, MD, PhD, the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research. “What if we could send in molecules before surgery to give surgeons optical, fluorescent signals to guide them?” That is the premise behind intraoperative molecular imaging.

Radiologists at Stanford have developed molecular agents that target specific biomarkers in tumor cells. They take a therapeutic antibody used to treat cancer, label it with a fluorescent tag to see where it binds, and then administer the agent by vein a day or two before surgery. The antibody attaches to the cancer and makes the tumor glow, allowing the surgeon to differentiate disease from normal tissue. These “molecular spies” can find cancer cells anywhere in the operative field that are not visible to the unaided eye. This greatly improves a surgeon’s ability to find and remove cancer and spare healthy tissue and organs. These agents can identify cancer in the primary site and in the surrounding lymph nodes, which helps make surgical removal less harmful and more targeted.

“Intraoperative molecular imaging has the potential to optimize surgical outcomes, improve the ability to distinguish normal from abnormal, and make it easier to identify if a cancer has spread to nearby lymph nodes,” said Eben Rosenthal, MD, professor of otolaryngology-head and neck surgery and radiology (molecular imaging program). Rosenthal has conducted bench to bedside development of these optical contrast agents. “We can see small, subclinical fragments of disease to see the margins better, and we can see tumor positive lymph nodes with a 99 percent predictive value. These agents can detect cancer not seen by the surgeon, improve complete resection and shorten surgery times.”

Sparing healthy tissue is a secondary benefit derived from this emerging technology. To ensure complete removal of a patient’s cancer, surgeons must take the cancerous cells as well as a margin of healthy tissue surrounding the cancer. But micro-invasion of surrounding tissue can make it difficult to determine an adequate tumor-free excision margin, often forcing surgeons to perform wide excisions including healthy tissue that may contain vital structures. Intraoperative molecular imaging helps surgeons see precise tumor margins during the operation to help them remove the tumor completely, with minimal safety margins.

“Molecular imaging greatly improves surgical precision,” said Gambhir, who is also a professor of radiology, and by courtesy of bioengineering, materials science and engineering. “Fluorescent signals can provide real-time guidance to assist surgeons in differentiating cancerous and normal tissues.”

This precision surgery tool can be further refined by using multiple, color-coded molecular agents, said Gambhir. Surgeons can wear goggles under dimmed lights to see the glowing molecules, or they can follow a color-coded image projected onto a screen as they remove glowing cells.

Stanford surgeons are currently using intraoperative molecular imaging in patients with head and neck, brain and pancreatic cancers, and beginning to test this technology in patients with skin cancer.